New insights into SUMOylation and NEDDylation in fibrosis DOI Creative Commons
Han Jin, Jun Wu,

Wen-Tao Kou

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 4, 2024

Fibrosis is the outcome of any abnormal tissue repair process that results in normal replacement with scar tissue, leading to persistent damage and cellular injury. During fibrosis, many cytokines chemokines are involved, their activities controlled by post-translational modifications, especially SUMOylation NEDDylation. Both these modifications entail a three-step activation, conjugation, ligation involves three kinds enzymes, namely, E1 activating, E2 conjugating, E3 ligase enzymes. participates organ fibrosis modulating FXR, PML, TGF-β receptor I, Sirt3, HIF-1α, Sirt1, while NEDDylation influences regulating cullin3, NIK, SRSF3, UBE2M. Further investigations exhibit therapeutic potentials SUMOylation/NEDDylation activators inhibitors against ginkgolic acid MLN4924 These demonstrate effects highlight as well potential candidates. In future, deeper needed identify novel substrates fibrosis; moreover, clinical determine can benefit patients. This review highlights function targets for fibrosis.

Language: Английский

SENP3 inhibition suppresses hepatocellular carcinoma progression and improves the efficacy of anti-PD-1 immunotherapy DOI Creative Commons
Peng Hui Wang, Jiannan Qiu, Yuan Fang

et al.

Cell Death and Differentiation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Abstract The importance of SUMOylation in tumorigenesis has received increasing attention, and research on therapeutic agents targeting this pathway progressed. However, the potential function during hepatocellular carcinoma (HCC) progression underlying molecular mechanisms remain unclear. Here, we identified that SUMO-Specific Peptidase 3 (SENP3) was upregulated HCC tissues correlated with a poor prognosis. Multiple functional experiments demonstrated SENP3 promotes malignant phenotype cells. Mechanistically, deSUMOylates RACK1 subsequently increases its stability interaction PKCβII, thereby promoting eIF4E phosphorylation translation oncogenes, including Bcl2, Snail Cyclin D1. Additionally, tumor-intrinsic infiltration tumor-associated macrophages (TAMs) while reducing cytotoxic T cells to facilitate immune evasion. CCL20 via /eIF4E axis. Liver-specific knockdown significantly inhibits liver chemically induced model. inhibition enhances efficacy PD-1 blockade an mouse Collectively, plays cell-intrinsic cell-extrinsic roles evasion by modulating oncogene cytokine translation. Targeting is novel target for boosting responsiveness immunotherapy.

Language: Английский

Citations

1
SUMO-Specific Peptidase 5 Promotes Oesophageal Squamous Cell Carcinoma Growth through the NF-κB-SLC1A3 Axis DOI Creative Commons

Chaoxiang Du,

Yunfan Hu,

Xinyu Yang

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 22, 2025

Background: This study investigates the role of small ubiquitin-like modifier (SUMO)-specific peptidase 5 (SENP5), a key regulator SUMOylation, in esophageal squamous cell carcinoma (ESCC), lethal disease, and its underlying molecular mechanisms. Methods: Differentially expressed genes between ESCC mouse oesophageal cancer tissues normal were analysed via RNA-seq; among them, SENP5 expression was upregulated, this gene selected for further analysis. Immunohistochemistry western blotting then used to validate increased protein level both human samples. The Kaplan‒Meier method multivariate analysis analyse relationship prognosis. Stable SENP5-knockdown (KD) lines conditional knockout (cKO) mice established verify biological function SENP5. Further RNA-seq comparisons short hairpin (shSENP5)- negative control (shNC)-transfected conducted, nuclear factor kappa B (NF-κB)—SLC1A3 axis identified through bioinformatics correlation with signalling pathway components validated real-time quantitative PCR (qPCR), (WB), immunoprecipitation. Results: Our revealed that upregulated samples, clinical data high poor patient knockdown inhibited tumorigenesis growth vivo suppressed proliferation, migration, invasion vitro. also enhanced SUMO1-mediated SUMOylation NF-kappa-B inhibitor alpha (IκBα), thereby inhibiting activation NF-κB–SLC1A3 axis, which subsequently suppresses energy metabolism impedes progression. Conclusions: Suppression slows development by NF-κB‒SLC1A3 IκBα. research suggests could serve as prognostic indicator target therapeutic intervention patients.

Language: Английский

Citations

0
SUMOylated hnRNPM suppresses PFKFB3 phosphorylation to regulate glycolysis and tumorigenesis DOI
Yi Zhong, Huanbin Zhao,

M. Lian

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217573 - 217573

Published: Feb. 1, 2025

Language: Английский

Citations

0
Recent advances in PROTAC-based antiviral and antibacterial therapeutics DOI
Can Zhou, Shiwei Yang, Jun Wang

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108437 - 108437

Published: April 1, 2025

Language: Английский

Citations

0
Identification of USP39 as a prognostic and predictive biomarker for determining the response to immunotherapy in pancreatic cancer DOI Creative Commons
Jiahui Yuan,

Xu Beibei,

Yongcheng Su

et al.

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 22, 2025

Ubiquitin-Specific Protease 39 (USP39) has been implicated in numerous malignancies, however, its pathogenic mechanisms and impact on the tumor immune microenvironment (TIME) remain incompletely characterized. Based The Cancer Genome Atlas (TCGA) Genotype-Tissue Expression (GTEx) databases, we investigated diagnostic prognostic values of USP39 across various cancer types. Additionally, examined correlation between expression immune-related gene signature, cell infiltration pattern, microsatellite instability (MSI), mutation burden (TMB). This study specifically focused exploring clinical relevance molecular functions pancreatic adenocarcinoma (PAAD), with particularly emphasis role shaping TIME modulating responses to immunotherapy. results demonstrated that evaluated significantly correlated advanced stage unfavorable outcomes multiple types, most notably PAAD. Functional enrichment analysis indicated potentially promotes progression through oncogenic signaling cascades. In vitro experimental validation confirmed knockdown inhibited migration proliferation cells while inducing apoptosis. identified significant positive correlations checkpoint molecules, prominent Furthermore, observed associations TMB 16 types MSI 11 suggesting heightened may enhance responsiveness immunotherapeutic interventions. Collectively, our findings establish as a valuable biomarker both utility especially PAAD, underscoring potential promising therapeutic target for Clinical trial number Not applicable.

Language: Английский

Citations

0
SUMOylation at the crossroads of gut health: insights into physiology and pathology DOI Creative Commons

XueNi Ma,

Muyang Li, Guoqing Qi

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 19, 2024

SUMOylation, a post-translational modification involving the covalent attachment of small ubiquitin-like modifier (SUMO) proteins to target substrates, plays pivotal role at intersection gut health and disease, influencing various aspects intestinal physiology pathology. This review provides comprehensive examination SUMOylation's diverse roles within microenvironment. We examine its critical in maintaining epithelial barrier integrity, regulating immune responses, mediating host-microbe interactions, thereby highlighting complex molecular mechanisms that underpin homeostasis. Furthermore, we explore impact SUMOylation dysregulation disorders, including inflammatory bowel diseases colorectal cancer, implications as potential diagnostic biomarker therapeutic target. By integrating current research findings, this offers valuable insights into dynamic interplay between health, paving way for novel strategies aimed restoring equilibrium combating associated pathologies.

Language: Английский

Citations

3
The role of ubiquitin-conjugating enzyme in the process of spermatogenesis DOI Creative Commons
Peng Lv, Jihong Liu, Xiaming Liu

et al.

Reproductive Biology and Endocrinology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 28, 2024

The ubiquitination is crucial for controlling cellular homeostasis and protein modification, in which ubiquitin-conjugating enzyme (E2) acts as the central player system. Ubiquitin-conjugating enzymes, have special domains that catalyse substrates, sequence discrepancies modulate various pathophysiological processes different cells of multiple organisms. E2s take part mitosis primordial germ cells, meiosis spermatocytes formation mature haploid spermatids to maintain normal male fertility. In this review, we summarize types their functions during distinct stages spermatogenesis.

Language: Английский

Citations

3
SUMOylation substrate encoding genes as prognostic biomarkers in pancreatic ductal adenocarcinoma with functional assessment of SAF-B2 DOI Creative Commons
Xiangjun Wang, Chuanxin Yang, Yangming Liu

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 16, 2025

Pancreatic ductal adenocarcinoma (PDAC) is highly malignant with a poor prognosis, posing significant clinical challenges. SUMOylation, reversible post-translational modification, plays critical role in tumor progression, yet its prognostic significance PDAC remains unclear. We assessed SUMOylation expression patterns and function using Western blot the inhibitor TAK-981. Differentially expressed substrate encoding genes (DE-SSEGs) were identified from The Cancer Genome Atlas (TCGA) Genotype-Tissue Expression Project (GTEx) datasets. A SUMOylation-based model, Sscore, was constructed LASSO Cox regression. Additional analyses included somatic mutation, immune infiltration, TIDE, drug sensitivity, single-cell RNA sequencing. of SAFB2 validated vitro. cells showed elevated inhibition reduced cell proliferation. Sscore based on DE-SSEGs (CDK1, AHNAK2, SAFB2), predicted overall survival correlated genome variation, sensitivity. Single-cell analysis further confirmed link between high malignancy. SAFB2, as pivotal gene within significantly downregulated tissues lines; overexpression shown to inhibit proliferation, migration, invasion by suppressing Wnt/β-Catenin signaling pathway. This study underscores introduces tool. potential suppressor, offering new therapeutic targets for PDAC.

Language: Английский

Citations

0
The Research Progress of Metformin Regulation of Metabolic Reprogramming in Malignant Tumors DOI
Qihai Sui,

Huiqiang Yang,

Zhengyang Hu

et al.

Pharmaceutical Research, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Language: Английский

Citations

1
Inhibition of SENP5 reduces brain injury in TBI rats by regulating NEDD4L/TCF3 axis DOI

Minjun Wei,

Tao Hong, Ying Liu

et al.

International Journal of Neuroscience, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 10

Published: May 7, 2024

The underlying mechanism of SENP5 influences neuronal regeneration and apoptosis in the context TBI remains largely unexplored.

Language: Английский

Citations

0